Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MULTIPLE SCLEROSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,045 records · Page 58Linked to original sources
PubMed2006

The epidemiology of multiple sclerosis in Europe.

Multiple sclerosis (MS) is a chronic and potentially highly disabling disorder with considerable social impact and economic consequences. It is the major cause of non-traumatic disability in young adults. The social costs associated with MS are high because of its long duration, the early loss of productivity, the need for assistance in activities of daily living and the use of immunomodulatory treatments and multidisciplinary health care. Available MS epidemiological estimates are aimed at providing a measure of the disease burden in Europe. The total estimated prevalence rate of MS for the past three decades is 83 per 100,000 with higher rates in northern countries and a female:male ratio around 2.0. Prevalence rates are higher for women for all countries considered. The highest prevalence rates have been estimated for the age group 35-64 years for both sexes and for all countries. The estimated European mean annual MS incidence rate is 4.3 cases per 100,000. The mean distribution by disease course and by disability is also reported. Despite the wealth of epidemiological data on MS, comparing epidemiological indices among European countries is a hard task and often leads only to approximate estimates. This represents a major methodological concern when evaluating the MS burden in Europe and when implementing specific cost-of-illness studies.

Disability Evaluation↗
PubMed2005

The CTLA4 +49 A/G*G-CT60*G haplotype is associated with susceptibility to multiple sclerosis in Flanders.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system white matter characterized by inflammation, demyelination and axonal damage. The cytotoxic T lymphocyte antigen-4 (CTLA-4) protein plays a key role in the down-regulation of T cell activation. We analysed the CTLA4 +49A/G and CT60 polymorphisms in a cohort of 120 MS trio families recruited from the Flanders region in Belgium. Both polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (RFLP). The +49 G-allele was significantly more transmitted to affected probands (P = 0.005). No transmission distortion was observed for the CT60 polymorphism. Haplotype analysis revealed significant overtransmission of the +49 A/G*G-CT60*G haplotype (P = 0.0025), and undertransmission of the +49 A/G*A-CT60*G haplotype (P = 0.015). The CTLA4 gene has been the focus of intense investigation in MS. Of 15 recently published papers, only six reported significant associations of various CTLA4 polymorphisms with MS, with the remainder being negative. Ours is the first report investigating the CT60 polymorphism in MS. Our data highlight a need for further scrutiny of the CTLA4 gene in MS.

Adult↗
PubMed1998

Choosing drug therapy for multiple sclerosis. An update.

Multiple sclerosis (MS) is an immunologically mediated disorder in which inflammation and demyelination of the central nervous system white matter are prominent features, resulting in various neurological signs and symptoms. In most patients, the course of the disease is initially characterised by relapses and remissions. In patients with chronic disease there is a tendency towards a gradually progressive disease course. MS relapses can best be treated with a course of high dose intravenous methylprednisolone. In ambulatory patients with relapsing remitting MS, partial prevention of relapses can be achieved by the use of interferon-beta-1a or -1b, whereas there is (as yet less convincing) evidence that glatiramer acetate (copolymer-1) might also be effective. At this time, there is no proof that these drugs are effective in patients with progressive MS, although trial results are expected to be available soon. In patients with rapidly progressive disease, it might be worth considering the effect of methotrexate. Future treatment options include new strategies to interfere with disease-relevant, specific or nonspecific immune mechanisms as well as drugs that might promote remyelination. In spite of the advances that have been made over the past few years, symptomatic treatment, including a multidisciplinary rehabilitation approach, remains the mainstay of treatment of the majority of MS patients.

Anti-Inflammatory Agents↗
PubMed2006

[Pathophysiology of multiple sclerosis].

Patients with multiple sclerosis (MS) can exhibit an exceptionally wide variety of symptoms. This is largely due to the semi-random distribution of the lesions in the central nervous system (CNS). Most lesions occur in apparently "silent" areas in the brain, and so cause no detectable symptoms. The disease is therefore much more active than a mere clinical monitoring would suggest. Most symptoms are related to a loss of function. During the relapses, this is due to a failure of axonal conduction at the site of the lesion(s). The conduction block is caused by the local demyelination which prevents the saltatory conduction but also seemingly, to some extend, by the inflammation per se. Remissions are related to a recovery of function of the affected axons owing to a spreading of sodium channels along the demyelinated axolemma but also to cerebral functional plasticity and remyelination. However, nerve conduction remains slower and less secure than normal, easily altered by physico-chemical changes such as the increase in body temperature (Uhthoff's phenomenon). Remission is incomplete when the lesion has led to axonal transaction and therefore axonal loss. Progression in MS is mainly related to "slow-burning" diffuse and chronic axonal loss in a toxic inflammatory milieu. Lastly, some symptoms in MS are so-called "positive" arising from an acquired hyperexcitability of demyelinated axons and occur either spontaneously (e.g. paresthesias) or mechanically (e.g. Lhermitte's sign).

Axons↗
PubMed2004

Measurement of neutralizing antibodies to interferon beta in patients with multiple sclerosis.

Treatment of multiple sclerosis (MS) with interferon beta (IFNbeta) can be associated with the development of binding antibodies (BAbs) and neutralizing antibodies (NAbs). NAbs are a subset of BAbs that prevent IFNbeta from effectively binding to or activating its receptor, thereby blocking its biologic effects and inhibiting its therapeutic effects. Several factors can affect the incidence and titers of NAbs that develop to IFNbeta, including the type of IFNbeta preparation used for treatment. One of the major limitations to evaluating the relative importance of these factors is the variation in assays used to detect IFNbeta antibodies. Two major types of assays are used to detect antibodies to IFNbetas: [1] binding assays, which measure the ability of antibodies in patients' sera to bind to IFNbeta; and [2] neutralization assays (or bioassays), which measure the ability of patients' sera to neutralize the biologic effects of IFNbeta. Assays used to detect NAbs differ in their sensitivity and specificity, and there can be high variability between laboratories in how these assays are performed (e. g., types of cells, quantity of IFNbeta). This article reviews assays currently used for detecting NAbs to IFNbeta and discusses the development of an international standard NAb assay. The myxovirus resistance protein A (MxA) assay is recommended as the standard assay for the quantification of NAbs providing availability of reagents.

Animals↗
PubMed1991

The function of the CD2 protein is abnormal in multiple sclerosis.

In active multiple sclerosis (MS), T cell adhesion to sheep red blood cells (SRBC) is deficient. The CD2 protein mediates adhesion to SRBC. Since ligands that bind CD2 can activate T cells, we studied adhesion and activation through CD2 in leukocytes from MS patients. Mononuclear cells (MNC) from patients with MS formed markedly fewer avid T cells (TA; T cells binding greater than or equal to 10 SRBC) than MNC from controls. CD2 antigen expression as measured by FACS analysis on T cells and on T cell subsets was equivalent in MS and controls and rose to a comparable extent in both groups after cell activation; yet activated MS MNC continued to form fewer TA than control cells. Avid rosette formation may be reduced by prostaglandins (PG) secreted by monocytes. Exposure to PG in vitro decreased TA% only in controls, suggesting refractoriness to exogenous PG in MS, perhaps because endogenous PG had already acted. The finding that indomethacin increased TA in MS cells favors this formulation. MNC were activated through CD2 using mAb 9-1 paired with mAb 9.6. Proliferation was significantly diminished in MNC from MS patients compared to MNC from normal controls. Thus, even though T cell membrane expression of CD2 appeared normal in MS, adhesion to SRBC and activation through the CD2 protein were defective.

Alprostadil↗
PubMedDate not supplied

Acute renal failure associated with dysfunctioning detrusor muscle in multiple sclerosis.

Patients with multiple sclerosis (MS) typically have neurogenic lower urinary tract dysfunction. Most patients present with bladder hyperreflexia and failure to empty the bladder secondary to detrusor-distal sphincter dyssynergia. This case study is unique in the literature in reporting on a patient presenting with acute renal failure (ARF) due to vesico-sphincter dysfunction associated with MS. A 64-year-old man with MS presented in the emergency department with the chief complaint of a marked decrease in urinary output for 2 days and weakness. He had been treated for MS for 7 years. A mass compatible with a full bladder was palpated in the suprapubic region on examination. Digital rectal examination disclosed grade I-Il prostate hypertrophy. Urinary catheters were inserted and urinary output was monitored. The residual urine was drained and recorded as 1100 mL. Initial laboratory findings, such as the BUN/creatinine ratio, urinary sodium concentration, and urine gravity, were compatible with ARF. The patient recovered rapidly in 24 hours following urinary catheterization and prompt medication in the emergency department. He was admitted to the neurology ward with a diagnosis of acute urinary outflow obstruction resulting in ARF due to detrusor dysfunction complicating an MS attack. ARF may complicate the course of patients with MS and associated detrusor-external sphincter dyssynergia. Renal recovery of these patients may be facilitated by urinary catheterization and supportive treatment.

Acute Kidney Injury↗
PubMed2002

Autonomic instability, as measured by pupillary unrest, is not associated with multiple sclerosis fatigue severity.

Multiple sclerosis (MS) fatigue is one of the most common symptoms in MS, but its pathophysiology is still not understood Sympathovagal imbalance was suggested as a reason for fatigue in chronic fatigue syndrome. We examined the role of an imbalance in the central autonomic nervous system (ANS) as a cause of MS fatigue in 51 MS patients and a control group of 22 healthy volunteers. Fatigue was assessed with the revised MS Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Depression was evaluated with the Beck Depression Inventory (BDI). Disintegration of the central ANS expressed by pupillary fatigue waves was measured with pupillography and documented in the pupillary unrest index (PUI). All subjects had less than five points on the seven-point Stanford Sleepiness Scale and were therefore not sleepy. MS patients had significant higher mean FSS scores (p=0.001) and mean MFIS scores (p=0.003) than our control group. Mean BDI scores were significant higher (p=0.001) in the MS group, but were in the lowest score range (0-10 points) in both groups. Surprisingly, we found a statistically significant inverse correlation between PUI values and either FSS scores (p=0.001; r=-0.521) or MFIS scores (p=0.002; r=-0.423) in the MS group, but not in healthy participants. We therefore conclude that autonomic instability, as measured by pupillary unrest is not associated with MS fatigue severity.

Adolescent↗
PubMed1991

Multiple sclerosis: changing times.

Multiple sclerosis (MS) is distributed about the world in three zones of high, medium, and low frequency. All high- and medium-risk areas are among predominantly white populations. Migration studies indicate MS is already acquired by age 15 in high-risk endemic areas and that low-to-high migrants increase their risk from age 11 years. Therefore MS is an environmental disease ordinarily acquired in adolescence with a long incubation before symptom onset. Susceptibility is limited to the period from about age 11 to 47. In general, MS death rates have been declining over time while prevalence rates have increased. Incidence rates have also increased, however, in: northeastern Scotland; Turku, Finland; Hordaland, Norway; Rochester, Minn.; Lower Saxony; several areas of Italy. Incidence was unchanged in northernmost Norway. Conversely, incidence and prevalence rates have decreased in the Shetland-Orkneys; there was a cyclical pattern in incidence in Rostock, GDR; and there was a transient doubling of incidence in Iceland in the post-World War II decade. In the Faroe Islands, MS was absent before 1943 when a major point-source epidemic began, reaching an incidence rate of 10 per 100,000 population in 1945. This was followed by two consecutively smaller epidemics with respective peaks each about 12 years later, and there is now a new epidemic IV on these islands. Explanations for changing incidence of MS over time should bring us closer to solving the etiology of this disease.

Cross-Cultural Comparison↗
PubMed2004

Th1/Th2 cytokine patterns and clinical profiles during and after pregnancy in women with multiple sclerosis.

Pregnancy in multiple sclerosis (MS) patients is associated with a lower risk of progression and lower rate of exacerbation. These beneficial effects are reversed postpartum. Considering that the pathogenesis of MS appears to involve cell-mediated immune reactivity, and that pregnancy is accompanied by a depressed cell-mediated immunity, it has been proposed that the lower relapse rate and risk of progression of MS during pregnancy may be due to a pregnancy-associated down-regulation of cell-mediated immunity. In addition, pregnancy results in a shift towards a T helper (Th) 2 cytokine profile, which is presumably protective for MS. This study was aimed at investigating the relationship between clinical status of MS and cytokine levels in eight patients with MS who were followed through pregnancy and after delivery. Peripheral blood lymphocytes from these women were stimulated with a mitogen at different time points during and after gestation and the levels of Th1 cytokines (IFNgamma, TNFalpha) and Th2 cytokines (IL-4, IL-10) were estimated by ELISA. It was established that six of the eight MS patients studied showed a distinct shift from a Th2 cytokine bias during pregnancy towards a Th1 cytokine bias after delivery. These results suggest a possible association between decreased incidence of exacerbation of MS in pregnancy and a pregnancy-induced shift towards Th2 cytokine bias.

Adult↗
PubMedDate not supplied

Cognitive impairments in multiple sclerosis: a review.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Cognitive impairment (CI) may develop at any time during the course of the disease in the presence or absence of neurological disability. On the basis of comprehensive neuropsychological studies, there is now a consensus among investigators that 45 percent to 65 percent of MS patients suffer from some degree and form of cognitive difficulty. Features of CI include bradyphrenia; impaired attention, concentration and abstract reasoning; reduced manual speed and dexterity; deficits in memory retrieval; and language deficits in both the relapsing-remitting and progressive forms of MS. Impairments in all cognitive domains may result from the diffuse spread of microscopic pathology, although a preferential lobar distribution of plaques can present with a predominant deficit in the corresponding cognitive function. Nevertheless, the severity of CI best correlates with total microscopic and macroscopic disease burden of the brain as defined by recently developed magnetic resonance imaging (MRI) sequences. A disruption of connecting intercortical and subcortical pathways is likely to be the main cause of metabolic and functional abnormalities in neurons. However a direct toxic effect of soluble inflammatory products may also compromise neuronal function and survival. Early treatment of MS with interferons and copaxone can prevent or delay the onset of both neurological and cognitive disabilities by reducing the inflammatory activity and damage in the CNS. Until more powerful neuroprotective agents become available, simple neuropsychological screening and cognitive rehabilitation for memory and language impairments will remain important components in the care of MS patients.

Brain↗
PubMedDate not supplied

[The use of magnetic resonance imaging in the study of asymptomatic familial multiple sclerosis patients].

INTRODUCTION: Multiple sclerosis (MS) is the neurological non-traumatic disease that produces permanent incapacity in the young people with the greatest frequency. An almost total consensus exists on the implication of environmental and genetic factors in the pathogenesis of the disease. In a considerable percentage of patients, antecedent relatives of other cases of MS exist, who are separated by other healthy relatives sometimes. AIMS: We try to study the familial antecedents of the MS patients, to locate to the healthy members of the family including in the forced line of the possible genetic transmission of the disease and ruling out subclinical involvement by the use of magnetic resonance imaging (MRI). PATIENTS AND METHODS: We reviewed the familial antecedents of the MS patients followed by the MS Unit of the Service of Neurology of the Hospital Virgen Macarena of Seville. After the accomplishment of their genealogical trees, we identified the cases of familial MS. We locate and practice MRI on the healthy subjects of the family, who are in the genetic line of communication of the disease (obligate carriers). RESULTS AND CONCLUSIONS: We were able to identify 14 obligate carriers of the gene in 12 of the families. In the MRIs that were done, we found MS-compatible lesions in 10 subjects. These findings confirm the existence of silent forms of the disease, that make difficult the knowledge of the genetic implications in the pathogenesis of the disease.

Aged↗
PubMed1994

Cladribine in treatment of chronic progressive multiple sclerosis.

Chronic progressive multiple sclerosis (MS) is a severely disabling demyelinating disease in which autoimmune processes seem to have a major role. The nucleoside drug cladribine is a potent lympholytic agent with few side-effects. We have studied its efficacy and safety in a randomised double-blind trial. 51 patients (48 entered as matched pairs) received four monthly courses of 0.7 mg/kg cladribine or placebo (saline) given through a surgically implanted central line. Neurologists with no knowledge of which medication the patient was receiving examined the patients monthly and noted two rating scale scores (Kurtzke and Scripps). Cerebrospinal fluid and brain magnetic resonance imaging (MRI) examinations were done at 6 and 12 months. Average neurological scores, demyelinated volumes on MRI, and concentrations of oligoclonal bands in cerebrospinal fluid were stable or improved in the patients receiving cladrabine but continued to deteriorate in patients on placebo. Mean paired (placebo minus matched cladribine) differences at 12 months relative to baseline were 1.0 (SE 0.4) for the Kurtzke scores, -13.9 (2.3) for the Scripps scores, 4.57 (1.17) mL for demyelinated volumes, and 7.3 (3.3) arbitrary units for concentrations of oligoclonal bands. Cladribine was generally well tolerated and clinically significant toxicity occurred in only 1 patient, in whom severe marrow suppression developed with complete recovery after several months. 1 patient died of newly acquired hepatitis B, an event unlikely to be related to cladribine. We conclude that the immunosuppressive drug cladribine influences favourably the course of chronic progressive MS.

Adult↗
PubMed1994

Influence of infection on exacerbations of multiple sclerosis.

Exacerbations of multiple sclerosis (MS) are triggered by exogenous events, the best documented being viral upper respiratory infections (URIs), which can stimulate secretion of cytokines such as interferon-gamma (IFN-gamma) by immune cells. In conjunction with a recent clinical trial of systemic interferon-beta (IFN-beta) in relapsing-remitting MS, we studied the occurrence of viral infections and their correlation with MS attacks. Thirty patients kept daily logs, noting URI symptoms in themselves, family members, and co-workers. Patients were examined every 3 months, or whenever an attack of MS occurred, and were tested for antibodies to common upper respiratory pathogens. A strong correlation was found between MS attacks and URIs. There were 168 URIs in 2,792 patient-weeks, including 996 weeks at risk (the interval beginning 1 week before and ending 5 weeks after onset of URI symptoms) and 1,796 weeks not at risk. Nearly two-thirds of attacks occurred in periods at risk. Attack rates were 2.92 per year in weeks at risk compared to 1.16 per year in weeks not at risk, a significant difference (p < 0.001). High-dose interferon reduced the frequency of MS attacks, but had no effect on the number of URIs. Although a specific virus could not be incriminated, we concluded that URIs of presumed viral origin are an important trigger of MS attacks, and that treatment with IFN-beta reduces the attack rate, but not by preventing URIs. Rather, it may modulate responses to viral infection that would otherwise lead to immune activation and clinical symptoms.

Acute Disease↗
PubMed1999

B cell repertoire diversity and clonal expansion in multiple sclerosis brain lesions.

Multiple sclerosis (MS) lesions in the CNS are characterized by disseminated demyelination with perivascular infiltrates of macrophages, T cells, and B cells. To investigate the origin and characteristics of the B cell population found in MS plaque tissue, we performed molecular studies in 10 MS patients and 4 non-MS control samples. Ig transcripts from the perivascular infiltrated brain lesions were analyzed by complementary-determining region 3 spectratyping to ascertain the B cell heavy chain gene rearrangement repertoire expressed in MS brains. Significant rearrangement diversity and deviation from the normal Ig heavy (H) chain repertoire was observed. The cloning and sequencing of RT-PCR products from families VH1 and VH4 showed a correlation with the profiles obtained by spectratyping. Generally, restricted spectratyping patterns concurred with repetition of in-frame complementary-determining region 3 identical sequences. The analysis of heavy chain variable (VH), diversity (D), and joining (JH) gene segments revealed the increased usage of VH1-69, VH4-34, and VH4-39. Similarly, gene segments from families D2, D3, and JH4 were over-represented. The presence of restricted patterns of rearranged Ig mRNA within the plaque lesion suggests that Ab production in the demyelinating plaque is a local phenomenon and supports the idea that in MS an Ag-driven immune response might be responsible for demyelination.

Amino Acid Sequence↗
PubMed1993

The pathogenesis of multiple sclerosis. Additional considerations.

Multiple sclerosis (MS) is acquired as a systemic "trait" by individuals who are genetically susceptible. This condition does not involve the central nervous system (CNS) and is characterized by a state of hyperactive immunocompetent responsiveness. It develops as the result of an antigenic challenge by a viral protein, either from a viral infection or a vaccination. In order for MS to become a disease affecting the CNS, it is necessary for the blood-brain barrier's (BBB) impermeability to be altered. This is now a fully recognized fact. As a result of this change, the MS lesion, which consists of edema and inflammation occurs. It may but need not lead to demyelination. Several mechanisms can cause this increased permeability of the BBB. The role of the immune system, and in particular of T lymphocytes in initiating and continuing the process of lesion formation remains extremely controversial. In fact, there are unanswered questions regarding the actual target of MS: is it the myelin sheath itself or its forming cell, the oligodendrocyte, or is it the BBB itself leading to bystander demyelination? The role of mild, concussional trauma to the CNS in producing the alteration of the BBB and therefore acting as a trigger or facilitator in the development or enlargement of MS lesions in the CNS, is based on considerable clinical, neuropathological and experimental evidence. Along with another viral infection, it must be one of the commonest causes of progression of MS, and quite often leads to the onset of the clinical manifestations of an hitherto asymptomatic condition.

Amino Acid Sequence↗
PubMed2000

Performance of the SF-36, SF-12, and RAND-36 summary scales in a multiple sclerosis population.

BACKGROUND: Multiple sclerosis (MS) patients accumulate both physical and mental health problems along with disease progression. Valid and sensitive outcome measures are important to measure disease effects and the effect of treatment. OBJECTIVE: The objective of this study was to test the performance of the physical and mental summary scales of SF-36, SF-12, and RAND-36. METHODS: The scales were evaluated by comparing the scores of a cohort of 194 MS patients with general population data and using the Expanded Disability Status Scale (EDSS) and the Incapacity Status Scale-mental as criterion variables for physical functioning and mental health. RESULTS: All 3 physical summary scales were markedly reduced and correlated highly with the EDSS. The SF-36 mental summary score was only slightly reduced among MS patients (0.2 SD) compared with the general population, despite significantly reduced scores on all 4 health scales being most related to mental health and despite a high prevalence of mental health problems. This results from the poor physical functioning (mean scale score, 2.3 SD below the general population) and the orthogonal factor rotation used to derive independent measures of physical and mental health. Similar results were found for the SF-12. The nonorthogonal RAND-36 physical and mental summary scores were both markedly reduced. This is more compatible with the disease progression in MS and the results of the other measures of physical and mental health used in the study. CONCLUSIONS: The SF-36 and SF-12 mental health summary scales appear to overestimate mental health in people with MS.

Activities of Daily Living↗
PubMed2006

Functional response to active and passive ankle movements with clinical correlations in patients with primary progressive multiple sclerosis.

Patients with multiple sclerosis (MS) activate a more diffuse cortical network than do healthy subjects when they perform motor tasks. This brain functional reorganisation might contribute to the limiting of disability, but it is unclear whether there is a loss of regional activation in more advanced disease. The aim of this study was to assess whether functional reorganisation diminishes in more disabled patients with primary progressive (PP) MS. The differences in the fMRI response to active and passive movements of the dominant ankle of 13 patients and 16 controls were assessed. The relationships between functional activation and disability and brain lesion load and atrophy were investigated.Patients showed greater fMRI activation than controls with passive movements in the superior temporal gyrus, rolandic operculum, and putamen. The fMRI response to active and passive movements in the ipsilateral inferior frontal gyrus was lower in patients with greater disability and greater brain T2 lesion load, respectively. Furthermore, the fMRI activation with active movements in the contralateral cerebellum was lower in patients with worse mobility. The increased activity with passive movements in regions that participate in sensori-motor integration, such as the putamen, reflects true functional reorganisation, since passive movements induce brain activation through sensory afferents only. The inverse correlation between the fMRI response in regions that are associated with motor control, and clinical or MRI measures of disease progression, suggests that there is a loss of distributed activation in more disabled patients. This may inform future treatment strategies.

Adaptation, Physiological↗